Cosyrel

Per 5 mg/5 mg FC tab Bisoprolol fumarate 5 mg (equiv to bisoprolol 4.24 mg), perindopril arginine 5 mg (equiv to perindopril 3.395 mg). Per 5 mg/10 mg FC tab Bisoprolol fumarate 5 mg (equiv to bisoprolol 4.24 mg), perindopril arginine 10 mg (equiv to perindopril 6.790 mg).

Substitution therapy in adult patients adequately controlled w/ bisoprolol & perindopril given concurrently at same dose level for: HTN; stable CAD (in patients w/ history of MI &/or revascularization); stable chronic heart failure w/ reduced systolic left ventricular function (5/5 only).

1 tab once daily. Stabilize at the same dose level for at least 4 wk. Fixed dose combination not suitable for initial therapy. If change of posology is required, titration w/ individual components. Elderly Administer according to renal function. Hepatic impairment No dosage adjustment.

Should be taken on an empty stomach: Take in the morning before a meal.

Hypersensitivity to bisoprolol, perindopril or other ACE inhibitors. Acute heart failure or during episodes of heart failure decompensation requiring IV inotropic therapy; cardiogenic shock; 2nd or 3rd degree AV block (w/o pacemaker); sick sinus syndrome; SA block; symptomatic bradycardia & hypotension; severe bronchial asthma or COPD; severe forms of peripheral arterial occlusive disease or Raynaud's syndrome; untreated phaeochromocytoma; metabolic acidosis; history of angioedema associated w/ previous ACE inhibitor therapy; hereditary or idiopathic angioedema. Concomitant use w/ aliskiren-containing products in patients w/ DM or renal impairment (GFR <60 mL/min/1.73 m²); sacubitril/valsartan. Extracorporeal treatments leading to blood contact w/ negatively charged surfaces. Significant bilateral renal artery stenosis or artery stenosis to a single functioning kidney. Pregnancy (2nd & 3rd trimesters).

Hypotension: Initiation should be closely monitored in patients who have been vol depleted, who have severe renin-dependent HTN, w/ symptomatic heart failure, w/ or w/o associated renal insufficiency, w/ ischaemic heart or cerebrovascular disease. A transient hypotensive response is not a contraindication to further doses once BP has increased after vol expansion. Hypersensitivity/angioedema/intestinal angioedema: Stop treatment & monitor until complete resolution of symptoms. Therapy w/ β-blocker must be continued. Angioedema associated w/ laryngeal oedema may be fatal. Combination w/ sacubitril/valsartan (contraindicated due to the increased risk of angioedema). Sacubitril/valsartan must not be initiated until 36 hr after taking the last dose of perindopril therapy. Perindopril therapy must not be started until 36 hr after the last dose of sacubitril/valsartan. Concomitant use of ACE inhibitors w/ NEP inhibitors (eg, racecadotril), mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) & gliptins (eg, linagliptin, saxagliptin, sitagliptin, vildagliptin) may lead to an increased risk of angioedema (eg, swelling of the airways or tongue, w/ or w/o resp impairment). Caution should be used when starting racecadotril, mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) & gliptins (eg, linagliptin, saxagliptin, sitagliptin, vildagliptin) in a patient already taking an ACE inhibitor. Hepatic failure: Rarely, ACE inhibitors have been associated w/ a syndrome that starts w/ cholestatic jaundice & progresses to fulminant hepatic necrosis & (sometimes) death: Treatment should be discontinued if jaundice or marked elevations of hepatic enzymes. Higher risk of angioedema in Black patients. Nonproductive cough. Hyperkalaemia: Frequent monitoring of serum K if renal insufficiency, worsening of renal function, age (>70 yr), DM, dehydration, acute cardiac decompensation, metabolic acidosis, & concomitant use of K-sparing diuretics, K supplements, K-containing salt substitutes, drugs associated w/ increases in serum K & especially aldosterone antagonists or angiotensin-receptor blockers. Combination w/ lithium, K-sparing drugs, K supplements, K-containing salt substitutes, Ca antagonists, Class I antiarrhythmic drugs, centrally acting antihypertensive drugs: Not recommended. Dual blockade of the renin-angiotensin-aldosterone system (RAAS): Concomitant use of ACE-inhibitors, ARBs or aliskiren increases the risk of hypotension, hyperkalaemia & decreased renal function (including acute renal failure). Dual blockade of RAAS is not recommended. ACE inhibitors & ARBs should not be used concomitantly in patients w/ diabetic nephropathy. Abrupt cessation should be avoided. The posology should be decreased gradually, using the individual components, ideally over a period of 2 wk. Bradycardia: If resting heart rate drops <50-55 bpm & symptoms related to bradycardia, dose should be downtitrated using the individual components w/ an appropriate dose of bisoprolol. Patients w/ 1st degree AV block, aortic & mitral valve stenosis, hypertrophic cardiomyopathy, diabetes, strict fasting should use w/ caution. Patients w/ Prinzmetal’s angina: β-blockers may increase the number & duration of angina episodes. Renal impairment: Daily dose should be adjusted on CrCl. Monitor K & creatinine. In patients w/ bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, increases in blood urea & serum creatinine have been seen; w/ renovascular HTN, increased risk of severe hypotension & renal insufficiency. Renovascular HTN: Increased risk of hypotension & renal insufficiency in patients w/ bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Diuretics may be a contributory factor. Loss of renal function may occur (minor changes in serum creatinine) even in patients w/ unilateral renal artery stenosis. Patients w/ recent kidney transplantation, treated for heart failure w/ IDDM (type I), severely impaired renal & hepatic function, restrictive cardiomyopathy, congenital heart disease, haemodynamically significant organic valvular disease, or MI w/in the last 3 mth: No experience. Anaphylactoid reactions are reported in patients dialysed w/ high flux membranes; during LDL apheresis w/ dextran sulphate, rarely, patients have experienced life-threatening anaphylactoid reactions, temporarily w/hold therapy prior to each apheresis; during desensitization treatment, when ACE inhibitor temporarily w/held, these reactions have been avoided, but reappeared upon inadvertent rechallenge. Neutropenia/agranulocytosis/thrombocytopenia/anaemia: Extreme caution in patients w/ collagen vascular disease, immunosuppressant therapy, treated w/ allopurinol or procainamide, periodic monitor of WBC counts advised. Bronchospasm (bronchial asthma, obstructive airways diseases): Bronchodilating therapy should be given concomitantly. Peripheral arterial occlusive disease. Anaesth: If it is necessary to w/draw β-blocker before surgery, this should be done gradually & completed about 48 hr before anaesth. Treatment should be discontinued 1 day pre-op. Psoriasis: Carefully balance the benefits/risks. Phaeochromocytoma: Bisoprolol should be given w/ an α-receptor blocker. Thyrotoxicosis: Symptoms may be masked. Primary aldosteronism: Use not recommended in patients w/ primary hyperaldosteronism (not responding to drugs acting through inhibition of the renin-angiotensin system). Excipients: Na-free. May impair ability to drive or operate machinery. Not suitable in patients w/ renal impairment. Pregnancy: Stop treatment. If appropriate, start alternative therapy. Lactation. Elderly.

Bradycardia. Headache, dizziness, vertigo, dysgeusia, paraesthesia, visual impairment, tinnitus, worsening of heart failure, hypotension & effects related to hypotension, feeling of coldness or numbness in the extremities, cough, dyspnoea, abdominal pain, constipation, diarrhoea, nausea, vomiting, dyspepsia, rash, pruritus, muscle cramps, asthenia, fatigue. Eosinophilia, hypoglycaemia, hyperkalaemia, hyponatraemia, altered mood, sleep disorder, depression, somnolence, syncope, palpitations, tachycardia, AV-conduction disturbances, orthostatic hypotension, vasculitis, bronchospasm, dry mouth, angioedema of face, extremities, lips, mucous membranes, tongue, glottis &/or larynx, urticaria, photosensitivity reactions, pemphigoid, hyperhidrosis, muscular weakness, arthralgia, myalgia, renal insufficiency, erectile dysfunction, chest pain, malaise, peripheral oedema, pyrexia, increased blood urea & creatinine, fall. SIADH, rhinitis, nightmares, hallucinations, reduced tear flow, hearing disorders, flushing, hepatitis either cytolytic or cholestatic, hypersensitivity reactions (itching, flush, rash), psoriasis aggravation, potency disorders, acute renal failure, anuria/oliguria, increased hepatic enzyme, blood bilirubin & triglycerides. Agranulocytosis, pancytopenia, leukopenia, neutropenia, thrombocytopenia, haemolytic anaemia in patients w/ a congenital deficiency of G6PDH, confusion, conjunctivitis, arrhythmia, angina pectoris, MI & stroke possibly secondary to excessive hypotension in high-risk patients, eosinophilic pneumonia, pancreatitis, erythema multiforme, alopecia. β-blockers may provoke or worsen psoriasis or induce psoriasis-like rash, decreased Hb & haematocrit. Raynaud’s phenomenon.

Drugs increase the risk of angioedema: Sacubitril/valsartan, racecadotril, mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus), gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin). Drugs inducing hyperkalaemia: Aliskiren, K salts, K-sparing diuretics, ACE inhibitors, angiotensin-II receptors antagonists, NSAIDs, heparins, immunosuppressant agents eg, ciclosporin or tacrolimus, trimethoprim & co-trimoxazole (trimethoprim/sulfamethoxazole). Contraindicated: Aliskiren in diabetic or impaired renal patients, extracorporeal treatments. Not recommended: Centrally acting antihypertensives eg, clonidine & others (eg, methyldopa, moxonidine, rilmenidine), Class I antiarrhythmic drugs (eg, quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone), Ca antagonists of the verapamil type & to a lesser extent of the diltiazem type, Aliskiren, concomitant therapy w/ ACE inhibitor & ARB, estramustine, K-sparing diuretics (eg, triamterene, amiloride), K (salts), lithium. Requiring special care: Antidiabetic agents (insulins, oral hypoglycaemic agents), NSAIDs (including ASA ≥3 g/day), antihypertensive agents & vasodilators, TCAs/antipsychotics/anesth, sympathomimetics, Ca antagonists of the dihydropyridine type eg, felodipine & amlodipine, class-III antiarrhythmic drugs (eg, amiodarone), parasympathomimetic drugs, topical β-blockers (eg, eye drops for glaucoma treatment), digitalis glycosides, baclofen, non-K-sparing diuretics, K-sparing diuretics (eplerenone, spironolactone). To be taken into consideration: Mefloquine, MAOIs (except MAO-B inhibitors), gold.

ACE Inhibitors/Direct Renin Inhibitors / Beta-Blockers

C09BX02 - perindopril and bisoprolol ; Belongs to the class of ACE inhibitors and other combinations. Used in the treatment of cardiovascular disease.

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